Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I

MPS I Clinical Trial

Official title:

A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02702115
• Other study ID #: SB-318-1502
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 24, 2017
• Est. completion date: November 3, 2021

Study information

• Verified date: December 2022
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.

Description:

The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of iduronidase for the lifetime of an MPS I patient.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: November 3, 2021
• Est. primary completion date: November 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

• Male or female = 5 years of age

• Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)

Exclusion Criteria:

• Known to be unresponsive to ERT

• Neutralizing antibodies to AAV 2/6

• Serious intercurrent illness or clinically significant organic disease (unless secondary to MPS I)

• Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2

• Lack of tolerance to laronidase treatment with significant IARs or occurrence of anaphylaxis

• Markers of hepatic dysfunction

• Creatinine = 1.5 mg/dL

• Contraindication to the use of corticosteroids for immunosuppression

• Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use (topical treatment allowed)

• Participation in prior investigational drug or medical device study within the previous 3 months

• Prior treatment with a gene therapy product

• Elevated or abnormal circulating a-fetoprotein (AFP)

• Weight <20 kg at Screening Visit

Related Conditions & MeSH terms

• MPS I
• Mucopolysaccharidoses
• Mucopolysaccharidosis I

Intervention

Biological:
• SB-318
A single dose of each of the three components of SB-318 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.

Locations

Country	Name	City	State
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events	Number of Participants with Treatment-Emergent Adverse Events	Up to 36 months after the SB-318 infusion
Secondary	Effect of SB-318 on IDUA Activity	Change from baseline clinical laboratory in measurement of IDUA activity measured in leukocytes.	Baseline and Month 36 after the SB-318 infusion
Secondary	Effect of SB-318 on Urine Glycosaminoglycans (GAG) Levels	Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 24	Baseline and 24 months after the SB-318 infusion
Secondary	AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen	Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.	Up to 24 months after the SB-318 infusion